OBJECTIVE:Adverse childhood experiences (ACEs) play a pivotal role in alcohol use disorder (AUD), and evidence suggests that this role differs by sex. Neural alcohol cue reactivity may represent one pathway linking ACEs to alcohol craving and use. The authors examined whether cue reactivity is differentially associated with the relationship between ACEs and alcohol-related outcomes in males and females with AUD. METHODS:Functional MRI data were analyzed from 231 non-treatment-seeking individuals (40.7% female; mean age=39.1 years, SD=13.5) with mainly mild to moderate AUD (mean number of DSM-5 criteria, 3.92, SD=1.6) from a 12-month prospective multicenter study. ACEs were assessed via Childhood Trauma Screener score. Participants completed a functional MRI alcohol cue reactivity task, followed by ecological momentary assessment of daily craving and consumption. Linear regression, general linear models, and sex-moderated mediation examined associations among ACEs, brain activation, and alcohol outcomes. Sensitivity analyses controlled for age, AUD severity, baseline consumption, tobacco use, Brief Symptom Inventory score, and progesterone-to-estradiol ratio. RESULTS:Higher Childhood Trauma Screener scores were associated with significantly greater left superior frontal gyrus/anterior cingulate cortex (SFG/ACC) activation during alcohol-related cues than during neutral cues in females compared with males. This activation significantly predicted prospective daily craving only in females. Sex-moderated mediation showed opposing indirect effects of ACEs on craving via SFG/ACC activation (ab=path a × path b; females: ab=0.008, 95% CI=0.001, 0.022; males: ab=-0.013, 95% CI=-0.034, -0.002). Sensitivity analyses supported robust SFG/ACC activation and directional consistency after adjustment for covariates. CONCLUSIONS:Sex-specific prefrontal cue reactivity patterns suggest differential neural pathways linking ACEs to craving vulnerability in early AUD, particularly in females. The findings support sex-sensitive, trauma-informed intervention strategies.

Most original articles published in the medical literature report the results of multiple statistical tests. In a few simple cases, there is agreement on whether to adjust for the number of performed tests. For many cases encountered in practice, however, this is less clear, and the recommendations in the literature are contradictory, along different dimensions, or otherwise confusing. This lack of clear guidance may impair the conduct and interpretation of analyses, and encourage questionable research practices, ultimately jeopardizing the credibility of medical research. In this article, we refine, illustrate, and discuss a unifying guiding principle to assist both statisticians and applied researchers in deciding whether to adjust for multiple testing and, if so, over which set of tests. The principle is that multiple testing should be adjusted for if and only if authors, when reporting and interpreting their findings, put more emphasis on results of one or several of the tests because of their small p-value(s). We relate this principle to previously proposed rules and show how it can guide and clarify the choice of adjustment strategies in three complex multiple testing settings.

Introduction Despite well-established sex/gender differences in alcohol dependence, sex-/gender-adapted treatments are very rarely available in clinical practice. However, such strategies have the potential to enhance the effectiveness of psychopharmacotherapy. The paper aims to summarize the current state of knowledge. Methods This work is based on an extended literature search, including both backward and forward searches starting from two published non-systematic reviews (McKee et al., 2022; Kirsch et al., 2024). In addition to treatment efficacy regarding consumption outcomes, the side effect profiles of psychopharmacologic drugs for the postacute treatment of alcohol dependence are considered. In this paper the psychopharmaceuticals naltrexone, baclofen, disulfiram, and acamprosate are discussed. Results In summary, men may benefit more from naltrexone regarding drinking behavior. Women seem to respond better to baclofen than men, although its efficacy has generally been found to be inconsistent across studies and it is not approved for the treatment of alcohol dependence in Germany. Compared to men, women report poorer tolerability and more side effects when taking high dose baclofen and naltrexone. It is important to note that the findings are inconsistent, which highlights the complexity of sex/gender differences in the psychopharmacological treatment of alcohol dependence. No data is available on differential psychopharmacotherapy for individuals outside the binary sex/gender categories of "woman" or "man." Discussion In the future, patients with alcohol dependence may benefit from sex-/gender-adapted treatment approaches. Choosing a drug with the most favorable risk-benefit profile for the respective sex/gender plays a key role in improving outcomes. Significant research gaps still persist: most study populations neglect women and do not represent gender minorities. As a result, sex-/gender-related treatment differences cannot be reliably identified. Additionally, dimensional aspects of sex/gender, such as the effects of the menstrual cycle, are rarely considered in current research.

Purpose The Alcohol use disorder (AUD) (F10.X) is among the most common diagnoses in hospital treatments in Germany and cause around 10 billion euros direct costs every year. Treatment includes detoxification, withdrawal treatments, rehabilitation measures, and drug-based relapse prevention. Disulfiram, which causes an alcoholaversionon reaction, is used for relapse prevention. This retrospective analysis aimed to determine the therapeutic needs of patients in outpatient disulfiram treatment and identify predictors for long-term treatment success. Methods Data from 76 male and 25 female alcohol-dependent patients (mean age: 43.98 +/- 8.48 years) who participated in supervised disulfiram administration were examined. The influence of average weekly treatment duration on treatment success was determined using a single-factor analysis of variance with covariates (ANCOVA). . Results ANCOVA revealed that the lowest relapse rate occurred with a treatment duration of 70 minutes per week (divided into three 23,3-minute sessions) compared to a short weekly treatment time (20 Minutes per week, divided into three sessions; post-hoc analysis p=0.043.). Disulfiram proved particularly effective for patients with a duration of addiction of more than 20 years (p=0.038). Conclusion Supervised disulfiram administration is a valuable method for treatingAUD, especially for patients with a long history of AUD (20 years or more). Optimal treatment outcomes are achieved bya combination of medication monitoring, psychosocial support, and individualized treatment intensity adjustments.

Trotz der etablierten Geschlechterunterschiede bei Alkoholabhängigkeit sind geschlechterangepasste Therapien im Praxisalltag äußerst selten verfügbar. Solche Strategien haben jedoch das Potenzial, die Wirksamkeit der Psychopharmakotherapie zu verbessern. Diese Übersichtsarbeit soll einen Überblick zum aktuellen Wissensstand geben. Die Arbeit stützt sich auf eine erweiterte Literaturrecherche inklusive Backward- und Forward-Suche ausgehend von zwei publizierten unsystematischen Reviews (McKee et al. 2022, Kirsch et al. 2024). Neben der Wirksamkeit auf Konsumendpunkte wird das Nebenwirkungsprofil von Psychopharmaka zur Postakutbehandlung der Alkoholabhängigkeit in der Literatur analysiert. In dieser Arbeit werden die Psychopharmaka Naltrexon, Baclofen, Disulfiram und Acamprosat diskutiert. Zusammengefasst könnten Männer im Vergleich zu Frauen im Hinblick auf das Alkoholkonsumverhalten mehr von Naltrexon profitieren. Frauen hingegen könnten im Vergleich zu Männern besser auf Baclofen ansprechen, dessen Wirksamkeit sich in Studien jedoch als inkonsistent darstellt und das in Deutschland nicht zur Behandlung der Alkoholabhängigkeit zugelassen ist. Im Vergleich zu Männern berichten Frauen sowohl bei Baclofen in hohen Dosen als auch bei Naltrexongabe von einer schlechteren Verträglichkeit und mehr Nebenwirkungen. Die Ergebnisse sind jedoch inkonsistent, was die Komplexität von Geschlechterunterschieden bei der Psychopharmakotherapie von Alkoholabhängigkeit unterstreicht. Zu Personen außerhalb der binären Geschlechterkategorien „Frau“ und „Mann“ sind keine Daten zur differentiellen Psychopharmakotherapie vorhanden. Patient:innen mit Alkoholabhängigkeit könnten zukünftig von einer geschlechterangepassten Therapie profitieren. Dabei spielt die Auswahl eines Wirkstoffes mit einem möglichst günstigen Nutzen-/Nebenwirkungsprofil für das jeweilige Geschlecht eine entscheidende Rolle. In der Literatur existieren deutliche Forschungslücken. Die meisten Studienpopulationen vernachlässigen Frauen; Geschlechterminoritäten sind nicht repräsentiert. Folglich können Geschlechterunterschiede nicht reliabel identifiziert werden. Zudem werden in der Literatur dimensionale Aspekte von Geschlecht – wie beispielsweise Effekte des Menstruationszyklus – selten berücksichtigt.

Preliminary animal and human studies have shown that blood dihydrotestosterone concentrations are increased in males with alcohol use disorder, and 5α-reductase inhibitors, which decrease dihydrotestosterone concentrations, reduce alcohol consumption. To gain mechanistic insight, we studied the effects of reduced dihydrotestosterone concentrations following pharmacological 5α-reductase inhibition on alcohol cue-elicited brain activity and alcohol craving in males with problematic alcohol use. To this end, this randomized, placebo-controlled, crossover challenge experiment investigated associations between dihydrotestosterone concentrations and brain functional magnetic resonance imaging (fMRI) activity during exposure to visual alcohol cues and alcohol craving following a single dose of 5 mg finasteride versus placebo in 50 males with heavy episodic drinking. We used finasteride because it specifically inhibits 5α-reductase II activity, which is the main enzyme converting testosterone to dihydrotestosterone. Dihydrotestosterone concentrations were lower in the finasteride condition in comparison to the placebo condition, but not significantly associated with brain activation patterns or craving. In the exploratory analyses, we found higher brain activity during exposure to visual stimuli in the right and left caudate nuclei, the right superior frontal gyrus and the left insula in the finasteride condition versus the placebo condition. Moreover, finasteride versus placebo was associated with a higher wish to not drink alcohol. The results of this experimental study do not support the à priori hypothesis that dihydrotestosterone concentrations play a role in brain activation during exposure to visual alcohol cues, but indicate that finasteride effects may be mediated by other pathways. Future studies are requested to investigate the effects of reduced dihydrotestosterone concentrations over a longer time and to shed light on the molecular mechanisms underlying the here observed effects of finasteride. Trial Registration: DRKS00020569.

The many-analysts approach has demonstrated a surprising diversity in analytic choices and outcomes given a single research question and dataset. As a result, the approach has gained traction as a tool for revealing and understanding epistemic uncertainty and is increasingly used for purposes beyond exposing analytic variability alone, including testing hypothesized effects across analytic approaches, estimating parameters, and generating theoretical insight through analytic triangulation. Despite its growing popularity, practical guidance for the lead team on how to design, interpret, and synthesize many-analysts studies remains limited. In this perspective, we propose four solutions to four problems in many-analysts studies, with the goal of making fuller use of the rich information generated by these projects. To demonstrate the practical application of these solutions, we use data from the Many-Analysts Religion Project and the OSSC19 Crowdsourced Replication Initiative.

Alcohol use disorder (AUD) is considered a chronic disorder with a highly variable course. Understanding this variability is crucial for identifying factors associated with persistence versus spontaneous remission. We analysed data from N = 462 individuals with AUD in an observational longitudinal cohort study to identify factors associated with spontaneous remission. All participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AUD at study entry and were reassessed after 1 year, in which they were classified as being in spontaneous remission (n = 107), falling below the ≥ 2-criteria threshold for AUD (n = 87) or continuing to meet AUD criteria (n = 296). Groups were compared on socio-demographic, clinical and substance use variables at baseline and after 1 year. Additionally, we used machine learning models to identify baseline characteristics predicting a persistent course of AUD. Between-group comparisons revealed that individuals who experienced spontaneous remission reported significantly lower AUD severity (F(2,459) = 25.17, p < 0.001), lower levels of alcohol intake (F(2,459) = 8.31, p = 0.013) and fewer drinking days (F(2,459) = 11.91, p < 0.001) at baseline and after 1 year. Machine learning analysis demonstrated moderate classification performance (AUC = 0.679), with the Alcohol Use Disorders Identification Test (AUDIT) sum score being the most informative predictor for group classification. Our findings indicate significant differences between spontaneously remitted and non-remitted individuals on key alcohol-related variables, supporting the clinical validity of remission as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). In addition, baseline characteristics may help identify individuals at risk of persistent AUD, enabling earlier identification of those who may benefit from specialized treatment. TRIAL REGISTRATION: DRKS number: DRKS00020580.

Heavy episodic drinking (HED) is highly prevalent in men and a major risk factor for Alcohol Use Disorder (AUD). Previous studies indicated an influence of testosterone (T) on AUD, and dihydrotestosterone (DHT) was linked to alcohol consumption, impulsivity, and response inhibition. As the role of androgens in AUD and the modulation thereof is not fully understood, this study investigated the effect of a pharmacological reduction in DHT by inhibition of the 5-alpha reductase II through finasteride on brain activation and response inhibition during a stop signal task. Fifty males with HED participated in a randomized, placebo-controlled, double blind, cross-over, functional magnetic resonance imaging (fMRI) study. Participants received either 5mg finasteride or placebo. Full factorial (fMRI) and linear mixed were used to estimate whole-brain effects of DHT and T following finasteride and placebo on neural correlates of behavioral control ( N = 45 analyzable participants). Lower levels of DHT and higher levels of T were related to stronger neural activation in temporal regions during response inhibition for successful or unsuccessful stop-trails, respectively. However, no significant influence of hormone levels on behavioral data of the stop signal task was observed. Although the precise mechanisms underlying the effects of pharmacologically altered DHT levels on neural correlates of response inhibition remain unresolved, both DHT and T appear to be specifically associated with neural activation during response inhibition. These findings stimulate the development of novel therapeutic approaches and treatment options based on pharmaceutical modulation of androgens addressing problem drinking, and possibly AUD.

Alkoholbezogene Störungen (F10.X) sind in Deutschland eine der häufigsten Diagnosen bei Krankenhausbehandlungen und verursachen jährlich etwa 10 Milliarden Euro direkte Kosten. Die Behandlung umfasst Entgiftung, Entzugsbehandlung, Rehabilitationsmaßnahmen und medikamentöse Rückfallprophylaxe. Disulfiram, welches eine Alkoholaversionsvreaktion auslöst, wird zur Rückfallprävention eingesetzt. Ziel der retrospektiven Analyse war es, die therapeutischen Bedürfnisse von Patienten in der ambulanten Disulfirambehandlung sowie Prädiktoren für eine erfolgreiche Therapie zu ermitteln. Untersucht wurden 76 männliche und 25 weibliche alkoholabhängige Patienten (Durchschnittsalter: 43,98±8,48 Jahre), die an der supervidierten Disulfiramvergabe teilnahmen Der Einfluss der durchschnittlichen wöchentlichen Behandlungsdauer auf den Behandlungserfolg wurde mit einer einfaktoriellen Varianzanalyse mit Kovariaten (ANCOVA) berechnet. Die Ergebnisse der ANCOVA zeigten, dass bei einer Behandlungszeit von 70 Minuten pro Woche (aufgeteilt in drei Sitzungen à 23,3 Minuten) im Vergleich zu einer kurzen wöchentlichen Behandlungszeit (20 Minuten pro Woche, aufgeteilt auf drei Sitzungen) die geringste Rückfallrate auftrat (post hoc Analyse p=0,043). Disulfiram war darüber hinaus besonders effektiv für Patienten mit einer Dauer der Abhängigkeitserkrankung von mehr als 20 Jahren (p=0,038). Die supervidierte Disulfiramvergabe stellt eine wertvolle Methode in der Behandlung von Alkoholabhängigkeit dar, besonders für Patienten mit langjähriger Abhängigkeitserkrankung. Optimale Therapieergebnisse werden durch eine Kombination aus Medikamentenüberwachung, psychosozialer Unterstützung und individueller Anpassung der Behandlungsintensität erreicht.

ABSTRACT Alcohol craving and consumption fluctuate across the reproductive cycle in females with alcohol use disorder (AUD), suggesting that estrogen signaling contributes to disease vulnerability. Here, we investigated the role of estrogen receptor alpha (ERα; Esr1 ; ESR1 ) in alcohol seeking using complementary mouse and human approaches, as this receptor was previously identified as a risk factor for AUD. Female mice were characterized in an IntelliCage-based multidimensional AUD paradigm that stratifies individuals into AUD-prone and AUD-resistant phenotypes. Transcriptomic profiling of the amygdala revealed that Esr1 is a top transcription factor for differentially expressed genes in mice drinking alcohol, and the estrogen signaling pathway was deregulated specifically in AUD-prone mice. Although alcohol exposure did not alter overall Esr1 /ERα mRNA or protein abundance, both transcript and protein levels positively correlated with cue-induced alcohol seeking, indicating that inter-individual variation in ERα signaling predicts relapse-like behavior. Causal manipulations confirmed a functional role of ERα. Local knockdown of Esr1 in the basolateral amygdala reduced excitatory synaptic transmission, attenuated alcohol motivation, cue-induced seeking, and relapse drinking, and impaired cue-associated memory recall without affecting anxiety-like behavior. Similarly, ovariectomy decreased amygdala ERα expression, altered synaptic protein markers, and reduced alcohol-seeking behaviors, supporting regulation by endogenous ovarian hormones. Extending these findings to humans, ESR1 gene polymorphisms (rs6902771, rs11155819 and rs6557171) were associated with the probability of alcohol binge drinking and alcohol consumption days as well as craving and loss of control in real world in a longitudinal clinical cohort, while ESR1 mRNA blood levels were increased in women with AUD diagnosis. Together, these convergent molecular, circuit, behavioral, and genetic data identify ERα signaling in the amygdala as an important modulator of alcohol-seeking behavior induced by alcohol cue and relapse vulnerability, highlighting estrogen pathways as potential therapeutic targets and markers for AUD.

Increasing availability of large routinely collected datasets presents many possibilities to answer more questions about health and disease, and at a faster pace. These opportunities are exciting, but, without the necessary expertise, well intentioned researchers can unwittingly fall into traps that make their work indistinguishable from that of less well meaning researchers. This article describes important challenges that arise in the analysis of routinely collected data and offers mitigation strategies to improve the trustworthiness of experimental and observational studies with the aim of explanation or prediction using classical statistical methods or AI algorithms. It also provides a roadmap to support researchers in conducting analyses on routinely collected data that produce more reliable estimates.

The same dataset can be analysed in different justifiable ways to answer the same research question, potentially challenging the robustness of empirical science1-3. In this crowd initiative, we investigated the degree to which research findings in the social and behavioural sciences are contingent on analysts' choices. We examined a stratified random sample of 100 studies published between 2009 and 2018, in which, for one claim per study, at least five reanalysts independently reanalysed the original data. The statistical appropriateness of the reanalyses was assessed in peer evaluations, and the robustness indicators were inspected along a range of research characteristics and study designs. We found that 34% of the independent reanalyses yielded the same result (within a tolerance region of ±0.05 Cohen's d) as the original report; with a four times broader tolerance region, this indicator increased to 57%. Of the reanalyses conducted, 74% reached the same conclusion as the original investigation, 24% yielded no effects or inconclusive results and 2% reported the opposite effect. This exploratory study indicates that the common single-path analyses in social and behavioural research should not be simply assumed to be robust to alternative analyses4. Therefore, we recommend the development and use of practices to explore and communicate this neglected source of uncertainty.

INTRODUCTION:Pathological gambling (PG) is characterized by altered decision-making. Even though studies have investigated decision-making in patients with PG, the effects of win-contingent stimuli thereon are not well understood yet. METHODS:Thus, we conducted a study in patients with PG (n = 10) and healthy individuals (n = 14), who performed two versions of a slot machine gambling task with and without win-contingent cues, while decision-making and gaze fixations were assessed using high-resolution eye-tracking. RESULTS:Patients with PG showed higher rates of high-risk decisions, lower rates of rational choices and showed less visual attention to probability information, but increased visual attention toward gambling cues, compared to healthy individuals. In the presence of win-contingent gambling cues, participants needed significantly more time to decide between high-risk versus low-risk gambles and spent significantly less time watching the probability information. CONCLUSION:Findings highlight the relevance of gambling-associated cues in PG. Targeting altered cue-reactivity could contribute to normalizing risky decision-making in patients with PG.

Cigarette smoking is a prevalent and critical global health issue, with inconsistent findings for its effects on endogenous progesterone concentrations. This large multicentre study investigated the associations between various markers of smoking behaviour and plasma progesterone concentrations using a sex-segregating approach. We studied 747 males aged 18-65 years and 158 peri-/postmenopausal females aged 50-65 years and assessed differences in plasma progesterone concentrations between smokers and never-smokers and associations of plasma progesterone concentrations with the Fagerström Test for Nicotine Dependence (FTND) score, cigarette pack years, age at onset of regular smoking, number of cigarettes smoked daily, exhaled carbon monoxide (CO), plasma cotinine and the Questionnaire of Smoking Urges (QSU) score. In models adjusted for age, body mass index (BMI), years of education, Alcohol Use Disorder Identification Test (AUDIT) scores, intake of any medication and study centre, and after correction for multiple hypothesis testing, there were no significant differences in plasma progesterone concentrations between smokers and never-smokers, and no significant associations between any of the mentioned markers of smoking behaviour and plasma progesterone concentrations in either males or females. The results suggest that smoking behaviour has no substantial effect on plasma progesterone concentrations and is not an important confounder in studies investigating progesterone.

Background:Social contextual factors influence the onset and maintenance of substance abuse. Virtual reality (VR) provides a standardized method to present social stimuli and is increasingly used in addiction research. Objective:This study examines the influence of a smoking versus a nonsmoking agent in VR on craving in nicotine-dependent male participants. Our primary hypothesis was that the interaction with a smoking agent is associated with increased craving compared to a nonsmoking agent. We expected higher craving in the presence of an agent regardless of the agent's smoking status. Methods:Using a head-mounted display (Oculus Rift), 50 nicotine-dependent smokers were exposed to four VR conditions on a virtual marketplace: first without an agent, second and third with an agent who either smoked or did not smoke in randomized order, and fourth without an agent as a follow-up condition. Before the follow-up condition, participants smoked a cigarette. Craving was assessed with the Questionnaire of Smoking Urges and a visual analog scale within VR and after each session. We also examined anxiety and agitation (visual analog scale), immersion and presence with the igroup Presence Questionnaire, and salivary cortisol levels. Results:Results showed no significant difference in the participants' craving, anxiety, or agitation between the smoking and nonsmoking agent conditions. However, craving, anxiety, and agitation increased from the marketplace without an interacting agent to the conditions with an interacting agent, and decreased after smoking a cigarette. Immersion was low in all conditions and decreased over time. Salivary cortisol levels were highest at baseline and decreased over the course of the experiment. Conclusions:These findings suggest that the presence of an agent (as a contextual factor) may override the specific influence of proximal stimuli (burning cigarette). The low immersion highlights the challenges in developing effective VR environments for cue exposure.

INTRODUCTION:Evidence suggests a role of appetite-regulating hormones in alcohol use disorder. Reductions in acylated ghrelin levels are associated with reductions in craving and cue-induced brain activity. Ghrelin levels can be physiologically decreased by glucose intake, which therefore could be a treatment reducing craving and cue-induced brain activity in patients with alcohol use disorder, potentially mediated by acylated ghrelin. MATERIAL AND METHODS:80 males and females with alcohol use disorder participated in the randomized placebo-controlled crossover study, examining glucose intake as acute treatment to reduce craving. Changes in craving and ghrelin levels were assessed at eight time points. Of these, 43 participants attended fMRI measurements examining habituation to cue-induced brain activation over time. Craving and hormone levels over time were analyzed using linear mixed modeling, brain activation habituation over time using flexible factorial models. RESULTS:Models revealed a significant interaction effect (F(1,474.607)= 13.563, p < .001) between sex and treatment on craving, with lower craving values in males (difference in means=-.540, p = .016, 95 %CI: -.976, -.103) and higher craving in females (difference in means=.815, p = .005, 95 %CI:.243, 1.387) in the glucose compared to the placebo condition. In males, we found a significant effect of treatment (F(1,313.602)= 7.811, p = .006) and a trend, but no significant effect of acylated ghrelin (F(1,301.568)= 3.574, p = .060) on craving as well as greater habituation to cue-induced brain activation after glucose compared to placebo intake in right putamen (T(1,35)= 4.77, p = .019). Individual habituation slopes significantly predicted the difference in craving before and after the alcohol task (F(2,36)= 5.234, p = .010; B= -36.018, p = .027) in males. CONCLUSIONS:Glucose intake could be a short-term treatment for males with alcohol use disorder to reduce alcohol craving and cue-induced brain activation. Sex-specific differences should be considered to gain a better understanding of the underlying mechanisms and develop treatment options for females.

AIMS:Coronary artery disease (CAD) is a frequent comorbidity in lung transplant (LuTx) candidates. The impact of allogenic organ transplantation and the corresponding alterations in immune response on the progression of CAD remains poorly understood. In this study, we sought to analyze the effect of donor-recipient overall human leukocyte antigen (HLA) and HLA-DQ mismatch on cardiovascular outcomes following LuTx. METHODS AND RESULTS:This retrospective analysis of adult patients receiving lung transplantation at the LMU University Hospital between 2012 and 2018 included 310 patients, the majority of whom (67.4%) had undergone double lung transplantation. There were no significant differences in the incidence of the primary composite endpoint between patients with high/low HLA mismatches (22 [7.9%] vs. 4 [12.9%]; p = 0.311). Numerically higher rates of the primary endpoint, myocardial infarction, and cardiovascular death in the low HLA mismatch group can partially be explained by differences in baseline rates of CAD and coronary sclerosis. Notably, neither HLA-DQ mismatch nor the occurrence of rejection episodes or cytomegalovirus (CMV) infection was associated with the occurrence of cardiovascular events following transplantation. CONCLUSION:In this study cohort, high HLA mismatch and HLA-DQ mismatch were not associated with increased adverse cardiovascular events. Furthermore, neither transplant rejection nor CMV infection increased the risk for cardiovascular events. The high cardiovascular event rates following LuTx necessitate meticulous cardiovascular follow-up, irrespective of immunological matching.

Stress- and alcohol cues trigger alcohol craving and alcohol consumption in alcohol use disorder (AUD). However, their interactions on a physiological and psychological level and their effects on daily alcohol craving and alcohol use in real-life situations are not understood yet. We conducted a randomized-controlled experimental study to compare the effects of psychosocial stress against physical stress and a control intervention, each followed by an alcohol cue-exposure, on alcohol craving, subjective stress and saliva cortisol levels (main outcomes) in N = 121 individuals with AUD and collected data on daily alcohol use and craving during a 1-year ambulatory assessment phase. We applied linear mixed models to compare the effects of experimental interventions on the main outcomes and the relative contributions of the observed changes on the main outcomes to predicting stress and alcohol craving during the experiment and alcohol use and craving during the ambulatory assessment phase. Sequential exposure to psychosocial stress and alcohol cues induced higher cortisol levels (F(10,580) = 10.819, p < 0.001), subjective stress (F(2,117) = 10.520, p < 0.001) and alcohol craving (F(6,348) = 4.313, p < 0.001) compared to the exposure to physical stress and the control condition. Subjective stress reactivity was the most influential predictor of craving during the experiment (F(1,92) = 9.43, p = 0.003) and during the ambulatory phase (β = 0.16, p = 0.039) while cortisol levels predicted alcohol consumption in real-life settings (β = 9.76, p = 0.043). Our results highlight the impact of psychosocial stress on cue-induced craving and subjective and neuroendocrine stress responses and demonstrate links between subjective and neuroendocrine stress-reactivity and alcohol craving and alcohol use in real-life settings.